Blouquit Sabine, Regnier Agathe, Dannhoffer Luc, Fermanian Christophe, Naline Emmanuel, Boucher Richard, Chinet Thierry
UPRES EA220, Pathology Department, and Clinical Research Unit, UFR Paris Ile de France Ouest, Université de Versailles Saint Quentin en Yvelines, Boulogne, France.
Am J Respir Crit Care Med. 2006 Aug 1;174(3):299-305. doi: 10.1164/rccm.200506-987OC. Epub 2006 Apr 27.
Small airways constitute a major site of pathology in cystic fibrosis (CF) and provide most of the surface area of the conducting airways of the lung. Little is known, however, about the impact of CF on ion and fluid transport in small (bronchiolar) airways.
To describe the ion and fluid transport properties of CF bronchiolar epithelium.
Primary cultures of human bronchial and bronchiolar (non-CF and CF) epithelial cells were obtained. The bioelectric properties were studied in Ussing chambers and the airway surface liquid (ASL) height was measured with confocal microscopy.
Primary cultures of DeltaF508 CF bronchiolar epithelial cells displayed higher transepithelial resistance than non-CF cultures, whereas baseline short circuit current and amiloride-inhibitable short circuit current were similar in both preparations. The ASL height was significantly smaller in CF compared with non-CF preparations. In the presence of amiloride, addition of forskolin increased short circuit current in non-CF but not in CF bronchiolar cultures, and the ATP-induced increase in short circuit current was lower in CF than in non-CF cultures. Non-CF bronchiolar preparations displayed larger short circuit current and fluid secretion in responses to forskolin than non-CF bronchial preparations, suggesting that CFTR-dependent Cl(-) transport may play a more important role in the regulation of fluid transport in small airways than in large airways.
In CF small airways, defective Cl(-) secretion combined with unregulated (persistent) Na(+) absorption results in ASLdepletion.
小气道是囊性纤维化（CF）病理变化的主要部位，并且构成了肺传导气道的大部分表面积。然而，关于CF对小（细支气管）气道中离子和液体转运的影响却知之甚少。
描述CF细支气管上皮细胞的离子和液体转运特性。
获取人支气管和细支气管（非CF和CF）上皮细胞的原代培养物。在尤斯灌流小室中研究生物电特性，并用共聚焦显微镜测量气道表面液体（ASL）高度。
DeltaF508 CF细支气管上皮细胞的原代培养物显示出比非CF培养物更高的跨上皮电阻，而两种制剂中的基线短路电流和氨氯地平可抑制的短路电流相似。与非CF制剂相比，CF中的ASL高度明显更小。在存在氨氯地平的情况下，添加福斯高林可增加非CF细支气管培养物中的短路电流，但不能增加CF细支气管培养物中的短路电流，并且CF中ATP诱导的短路电流增加低于非CF培养物。与非CF支气管制剂相比，但非CF细支气管制剂对福斯高林的反应显示出更大的短路电流和液体分泌，这表明CFTR依赖性Cl⁻转运在小气道液体转运调节中可能比大气道中起更重要的作用。
在CF小气道中，Cl⁻分泌缺陷与不受调节（持续）的Na⁺吸收相结合导致ASL耗竭。
